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Primary and Booster Vaccination Study With a Pneumococcal Vaccine in HIV Infected, HIV Exposed Uninfected and HIV Uninfected Children 6 to 10 Weeks of Age.

Primary Purpose

Infections, Streptococcal

Status

Completed

Phase

Phase 3

Locations

South Africa

Study Type

Interventional

Intervention

Pneumococcal vaccine GSK1024850A

Tritanrix-HepB/Hib

measles

Rotarix

Local OPV

About this trial

This is an interventional prevention trial for Infections, Streptococcal focused on measuring Human Immunodeficiency Virus, Booster vaccination, Safety, Primary vaccination, Pneumococcal vaccine, Immunogenicity, Pneumococcal disease

Eligibility Criteria

6 Weeks - 10 Weeks (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Male or female subjects between, and including 6-10 weeks of age at the time of the first vaccination.
Subjects for whom the investigator believes that their parent(s)/guardian(s) can and will comply with the requirements of the protocol.
Written informed consent obtained from the parent(s)/guardian(s) of the child/ward.
Free of any known or suspected health problems (as established by medical history and clinical examination before entering into the study).

Exclusion Criteria:

Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of the study vaccines, or planned use during the study period.
A family history of hereditary immunodeficiency other than HIV infection.
Major congenital defects or serious chronic illness other than HIV infection.
For HIV infected infants: Moderately and severely symptomatic: stages III and IV according to latest version of WHO classification.
Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
Previous vaccination against diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, and/or Streptococcus pneumoniae.
History of, or intercurrent, diphtheria, tetanus, pertussis, and Haemophilus influenzae type b disease.
History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
History of any neurological disorders or seizures.
Acute disease at the time of enrolment.
Babies for which weight for age is < 3rd percentile at Visit 1, using standard growth charts, with the exception of HIV infected infants for which the decision of enrolment was left to the investigator's discretion.
Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal (GI) tract, intussusception (IS) or other medical condition determined to be serious by the investigator.
Gastroenteritis within 7 days preceding the study vaccine administration (warrants deferral of vaccination).

Sites / Locations

GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

HIV+/+ Group

HIV+/- Group

HIV- (3+1) Group

HIV- (EPI) Group

HIV- (2+1) Group

Arm Description

Infants born from a HIV positive mother and confirmed as HIV infected. Subjects received 3 primary doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered intramuscularly in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.

Infants born from a HIV positive mother and confirmed as HIV exposed uninfected. Subjects received 3 primary doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.

Infants born from a HIV negative mother and confirmed as HIV unexposed uninfected. Subjects received 3 primary doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.

Infants born from a HIV negative mother and confirmed as HIV unexposed uninfected.Subjects received 3 primary doses of Synflorix™ vaccine (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.

Infants born from a HIV negative mother and confirmed as HIV unexposed uninfected.Subjects received 2 primary doses (at 6 & 14 weeks of age at study Months 0 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.

Outcomes

Primary Outcome Measures

Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 Microgram Per Millilitre (µg/mL).

Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

Secondary Outcome Measures

Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes.

Concentrations were given in microgram per millilitre (µg/mL) and were expressed in geometric mean antibody concentrations. Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Data were collected post-Dose 3 at Month 3 and post-Dose 4 at Month 9 for the HIV+/+, HIV+/- and HIV- (3+1) groups, post-Dose 3 at Month 3 and at Month 9 for HIV- (3+0) group, and post-Dose 2 at Month 3 and post-Dose 3 at Month 9 for the HIV- (2+1) Group. The cut-off of the assay is 0.05 µg/mL.

Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes.

Concentrations were given in microgram per millilitre (µg/mL) and were expressed in geometric mean antibody concentrations. Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Data were collected post-Dose 4 at Month 23 for the HIV+/+, HIV+/- and HIV- (3+1) groups and post-Dose 3 at Month 23 for HIV- (3+0) and HIV- (2+1) groups. The cut-off of the assay is 0.05 µg/mL.

Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes.

Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Data were collected post-Dose 3 at Month 3 and post-Dose 4 at Month 9 for the HIV+/+, HIV+/- and HIV- (3+1) groups,post-Dose 3 at Month 3 and at Month 9 for HIV- (3+0) group, and post-Dose 2 at Month 3 and post-Dose 3 at Month 9 for the HIV- (2+1) Group. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titer of 8.

Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes.

Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Data were collected post-Dose 4 at Month 23 for the HIV+/+, HIV+/- and HIV- (3+1) groups and post-Dose 3 at Month 23 for HIV- (3+0) and HIV- (2+1) groups. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titer of 8.

Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A.

Concentrations were given in microgram per millilitre (µg/mL) and were expressed in geometric mean antibody concentrations. Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A. Data were collected post-Dose 3 at Month 3 and post-Dose 4 at Month 9 for the HIV+/+, HIV+/- and HIV- (3+1) groups,post-Dose 3 at Month 3 and at Month 9 for HIV- (3+0) group, and post-Dose 2 at Month 3 and post-Dose 3 at Month 9 for the HIV- (2+1) Group. The cut-off of the assay is 0.05 µg/mL.

Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A.

Concentrations were given in microgram per millilitre (µg/mL) and were expressed in geometric mean antibody concentrations. Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A. Data were collected post-Dose 4 at Month 23 for the HIV+/+, HIV+/- and HIV- (3+1) groups and post-Dose 3 at Month 23 for HIV- (3+0) and HIV- (2+1) groups. The cut-off of the assay is 0.05 µg/mL.

Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A.

Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A. Data were collected post-Dose 3 at Month 3 and post-Dose 4 at Month 9 for the HIV+/+, HIV+/- and HIV- (3+1) groups,post-Dose 3 at Month 3 and at Month 9 for HIV- (3+0) group, and post-Dose 2 at Month 3 and post-Dose 3 at Month 9 for the HIV- (2+1) Group. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titer of 8.

Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A.

Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A. Data were collected post-Dose 4 at Month 23 for the HIV+/+, HIV+/- and HIV- (3+1) groups and post-Dose 3 at Month 23 for HIV- (3+0) and HIV- (2+1) groups. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titer of 8.

Concentrations of Antibodies Against Protein D (PD) by ELISA

Concentrations of antibodies are presented as GMCs expressed as ELISA units per milliliter (EL.U/mL). The cut-off of the assay was 100 EL.U/mL. Data were collected post-Dose 3 at Month 3 and post-Dose 4 at Month 9 for the HIV+/+, HIV+/- and HIV- (3+1) groups,post-Dose 3 at Month 3 and at Month 9 for HIV- (3+0) group, and post-Dose 2 at Month 3 and post-Dose 3 at Month 9 for the HIV- (2+1) Group.

Concentrations of Antibodies Against Protein D (PD) by ELISA.

Concentrations of antibodies are presented as GMCs expressed as ELISA units per milliliter (EL.U/mL). The cut-off of the assay was 100 EL.U/mL. Data were collected post-Dose 4 at Month 23 for the HIV+/+, HIV+/- and HIV- (3+1) groups and post-Dose 3 at Month 23 for HIV- (3+0) and HIV- (2+1) groups.

Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT).

Concentrations of antibodies are presented as GMCs expressed as International units per millilitre (IU/mL) The cut-off of the assay is 0.1IU/mL.

Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT).

Concentrations of antibodies are presented as GMCs expressed as International units per millilitre (IU/mL). The cut-off of the assay is 0.1IU/mL.

Concentrations of Antibodies Against Bordetella Pertussis (BPT) by ELISA.

Concentrations of antibodies are presented as GMCs expressed as ELISA units per millilitre (EL.U/mL). The cut-off of the assay is 15 EL.U/mL.

Concentrations of Antibodies Against Bordetella Pertussis (BPT) by ELISA .

Concentrations of antibodies are presented as GMCs expressed as ELISA units per millilitre (EL.U/mL). The cut-off of the assay is 15 EL.U/mL.

Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP)

Concentrations of antibodies are presented as GMCs expressed as microgram per millilitre (µg/mL). The cut-off of the assay is 0.15 µg/mL.

Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP)

Concentrations of antibodies are presented as GMCs expressed as microgram per millilitre (µg/mL). The cut-off of the assay is 0.15 µg/mL.

Concentrations of Antibodies Against Hepatitis B Surface Antigen (HBs) by ELISA

Concentrations of antibodies are presented as GMCs expressed as milli-International units per milliliter (mIU/mL). The cut-off of the assay is 10 mIU/mL. As a decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL), the table showed results following partial or complete retesting/reanalysis

Concentrations of Antibodies Against Hepatitis B Surface Antigen (HBs) by ELISA.

Concentrations of antibodies were presented as GMCs expressed as milli-International units per milliliter (mIU/mL). The cut-off of the assay was 10 mIU/mL. As a decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL), the table showed results following partial or complete retesting/reanalysis

Concentrations of Antibodies Against Rotavirus Immunoglobulin A (Rotavirus IgA), by Rotarix Vaccination Status.

Concentrations of antibodies are presented as GMCs expressed as units per millilitre (U/mL). The cut-off of the assay is 20 U/mL. Data were collected for subjects who received 1, 2 doses or no Rotarix dose during the study.

Concentrations of Antibodies Against Measles

Concentrations of antibodies are presented as GMCs expressed as milli-International units per milliliter (mIU/mL).The cut-off of the assay is 150 mIU/mL.

Anti-LytC IgA and Anti-PhtD IgA Antibodies Concentrations in Salivary Samples

Salivary antibodies against selected common bacterial protein antigens. Salivary samples (1.0 mL) were collected by using an Oracol™ device consisting of a sponge (2 cm3) placed on a stick that was used to brush the teeth and gums to absorb the saliva. Salivary samples were sent to RMPRU (or GSK Biologicals' designated validated laboratory) where the sponge was centrifuged to extract the saliva and that was immediately stored at -70°C. The cut-off of the assay was 2.3 U/mL for anti-LytC IgA and 2.2 U/mL for anti PhtD IgA.

Number of Swabs With Positive Cultures of Haemophilus Influenzae and/or Streptococcus Pneumoniae (Vaccine Serotypes, Cross-reactive or Other Serotypes) and Other Bacterial Pathogens in the Nasopharynx.

Positive cultures of H. influenza* (HI) and S. pneumonia(SP) and other bacterial pathogens such as Moraxella catarrhalis(MC), Group A streptococci and Staphylococcus aureus (SA), identified in the nasopharynx at each swab time point: Month (Mth) 0 (Pre-vaccination time point at 6-12 weeks of age), Mth 3 (18 weeks of age), Mth 8 (9-10 Months of age), Mth 9 (10-11 Months of age), Mth 11 (12-13 Months of age), Mth 14 (15-18 Months of age), Mth 15 (16-19 Months of age) and Mth 23 (24-27 Months of age). *Data presented included only results from samples confirmed as positive for Hi/Non Typeable Hi after differentiation from H. haemolyticus by Polymerase Chain Reaction (PCR) assay

Number of Subjects With Acquisition of New Streptococcus Pneumoniae and Haemophilus Influenzae Strains Identified in Nasopharyngeal Swabs

Acquisition of new H. influenza* (HI) and S. pneumonia(SP) strains, identified in the nasopharynx at each swab time point: Month (Mth) 3 (18 weeks of age), Mth 8 (9-10 Months of age), Mth 9 (10-11 Months of age), Mth 11 (12-13 Months of age), Mth 14 (15-18 Months of age), Mth 15 (16-19 Months of age) and Mth 23 (24-27 Months of age). *Data presented included only results from samples confirmed as positive for Hi/Non Typeable Hi after differentiation from H. haemolyticus by PCR assay

Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs).

Solicited local AEs assessed were pain, redness and swelling. Any = incidence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling above 30 millimetre.

Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs).

General AEs = diarrhoea, drowsiness, irritability, loss of appetite, vomiting and fever (axillary ≥ 37.5 degrees Celsius). Any= Incidence of any symptom regardless of intensity grade or relationship to vaccination. Grade 3: drowsiness = prevented normal activity. irritability = crying that could not be comforted/ prevented normal activity. loss of appetite = not eating at all. diarrhoea: ≥ 6 looser than normal stools/day. vomiting: ≥ 3 episodes of vomiting/day. Fever = > 39.5°C Related = symptom assessed by the investigator as related to the vaccination.

Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs).

Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs).

Solicited general AEs = drowsiness, irritability, loss of appetite and fever (axillary ≥ 37.5 degrees Celsius). Any= Incidence of any symptom regardless of intensity grade or relationship to vaccination. Grade 3: drowsiness = prevented normal activity. irritability = crying that could not be comforted/ prevented normal activity. loss of appetite = not eating at all. Fever = temperature > 39.5°C Related = symptom assessed by the investigator as related to the vaccination.

Number of Subjects With Unsolicited AEs.

An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

Number of Subjects With Unsolicited AEs.

Number of Subjects With Serious Adverse Events (SAEs).

SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.

Full Information

NCT ID

NCT00829010

First Posted

January 22, 2009

Last Updated

July 11, 2018

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT00829010

Brief Title

Primary and Booster Vaccination Study With a Pneumococcal Vaccine in HIV Infected, HIV Exposed Uninfected and HIV Uninfected Children 6 to 10 Weeks of Age.

Official Title

Primary and Booster Vaccination Course in Human Immunodeficiency Virus (HIV) Infected Infants, HIV Exposed Uninfected Infants and Unexposed Uninfected Infants Receiving the Pneumococcal Vaccine GSK 1024850A.

Study Type

Interventional

2. Study Status

Record Verification Date

October 2017

Overall Recruitment Status

Completed

Study Start Date

February 17, 2009 (undefined)

Primary Completion Date

June 13, 2011 (Actual)

Study Completion Date

June 27, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

5. Study Description

Brief Summary

The purposes of this study: To evaluate the immunogenicity, safety and reactogenicity of pneumococcal vaccine GSK1024850A in HIV infected infants, HIV exposed uninfected infants and HIV unexposed uninfected infants following a 3-dose primary vaccination at 6, 10 and 14 weeks of age and following booster vaccination at 9-10 months of age. To evaluate the immunogenicity, safety and reactogenicity of pneumococcal vaccine GSK1024850A in HIV unexposed uninfected infants receiving either a 3-dose primary vaccination according to the EPI vaccination schedule at 6, 10 and 14 weeks of age with or without booster vaccination at 9-10 months of age or a 2-dose primary vaccination at 6 and 14 weeks of age followed by booster vaccination at 9-10 months of age. This study also aims to assess the impact of the pneumococcal vaccine GSK1024850A on nasopharyngeal carriage of S. pneumoniae and H. influenzae up to 24 months of age in all study participants.

Detailed Description

This protocol posting has been updated according to Protocol amendment 1, December 08

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Infections, Streptococcal

Keywords

Human Immunodeficiency Virus, Booster vaccination, Safety, Primary vaccination, Pneumococcal vaccine, Immunogenicity, Pneumococcal disease

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

489 (Actual)

8. Arms, Groups, and Interventions

Arm Title

HIV+/+ Group

Arm Type

Experimental

Arm Description

Arm Title

HIV+/- Group

Arm Type

Experimental

Arm Description

Arm Title

HIV- (3+1) Group

Arm Type

Experimental

Arm Description

Arm Title

HIV- (EPI) Group

Arm Type

Experimental

Arm Description

Arm Title

HIV- (2+1) Group

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Pneumococcal vaccine GSK1024850A

Intervention Description

Intramuscular injection, administered as 3 or 4 doses

Intervention Type

Biological

Intervention Name(s)

Tritanrix-HepB/Hib

Other Intervention Name(s)

DTPw-HBV/Hib

Intervention Description

Intramuscular injection, 4 doses

Intervention Type

Biological

Intervention Name(s)

measles

Intervention Description

Intramuscular injection, 2 doses

Intervention Type

Biological

Intervention Name(s)

Rotarix

Other Intervention Name(s)

HRV, Human rotavirus

Intervention Description

Oral, 2 doses

Intervention Type

Biological

Intervention Name(s)

Local OPV

Other Intervention Name(s)

oral poliovirus vaccine

Intervention Description

Oral 4 doses. Given at any time during the study, routinely given concurrently with DTPw-HBV/Hib vaccine

Primary Outcome Measure Information:

Title

Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 Microgram Per Millilitre (µg/mL).

Description

Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

Time Frame

1 month following primary immunization (post-Dose 3 at Month 3 for the HIV+/+ Group, HIV+/- Group, HIV- (3+1) Group, HIV- (3+0) Group and post-Dose 2 at Month 3 for the HIV- (2+1) Group)

Secondary Outcome Measure Information:

Title

Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes.

Description

Time Frame

At Month 3 and Month 9

Title

Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes.

Description

Concentrations were given in microgram per millilitre (µg/mL) and were expressed in geometric mean antibody concentrations. Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Data were collected post-Dose 4 at Month 23 for the HIV+/+, HIV+/- and HIV- (3+1) groups and post-Dose 3 at Month 23 for HIV- (3+0) and HIV- (2+1) groups. The cut-off of the assay is 0.05 µg/mL.

Time Frame

up to study end at Month 23 (24-27 months of age)

Title

Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes.

Description

Time Frame

At Month 3 and at Month 9

Title

Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes.

Description

Time Frame

up to study end at Month 23 (24-27 months of age)

Title

Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A.

Description

Time Frame

At Month 3 and Month 9

Title

Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A.

Description

Concentrations were given in microgram per millilitre (µg/mL) and were expressed in geometric mean antibody concentrations. Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A. Data were collected post-Dose 4 at Month 23 for the HIV+/+, HIV+/- and HIV- (3+1) groups and post-Dose 3 at Month 23 for HIV- (3+0) and HIV- (2+1) groups. The cut-off of the assay is 0.05 µg/mL.

Time Frame

up to study end at Month 23 (24-27 months of age)

Title

Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A.

Description

Time Frame

At Month 3 and at Month 9

Title

Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A.

Description

Time Frame

up to study end at Month 23 (24-27 months of age)

Title

Concentrations of Antibodies Against Protein D (PD) by ELISA

Description

Time Frame

At Month 3 and at Month 9

Title

Concentrations of Antibodies Against Protein D (PD) by ELISA.

Description

Time Frame

up to study end at Month 23 (24-27 months of age)

Title

Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT).

Description

Concentrations of antibodies are presented as GMCs expressed as International units per millilitre (IU/mL) The cut-off of the assay is 0.1IU/mL.

Time Frame

1 month following primary immunization (at Month 3)

Title

Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT).

Description

Concentrations of antibodies are presented as GMCs expressed as International units per millilitre (IU/mL). The cut-off of the assay is 0.1IU/mL.

Time Frame

1 month after the booster dose of DTPw-HBV/Hib vaccine (at Month 15)

Title

Concentrations of Antibodies Against Bordetella Pertussis (BPT) by ELISA.

Description

Concentrations of antibodies are presented as GMCs expressed as ELISA units per millilitre (EL.U/mL). The cut-off of the assay is 15 EL.U/mL.

Time Frame

1 month following primary immunization (at Month 3)

Title

Concentrations of Antibodies Against Bordetella Pertussis (BPT) by ELISA .

Description

Concentrations of antibodies are presented as GMCs expressed as ELISA units per millilitre (EL.U/mL). The cut-off of the assay is 15 EL.U/mL.

Time Frame

1 month after the booster dose of DTPw-HBV/Hib vaccine (at Month 15)

Title

Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP)

Description

Concentrations of antibodies are presented as GMCs expressed as microgram per millilitre (µg/mL). The cut-off of the assay is 0.15 µg/mL.

Time Frame

1 month following primary immunization (at Month 3)

Title

Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP)

Description

Concentrations of antibodies are presented as GMCs expressed as microgram per millilitre (µg/mL). The cut-off of the assay is 0.15 µg/mL.

Time Frame

1 month after the booster vaccination (at Month 15)

Title

Concentrations of Antibodies Against Hepatitis B Surface Antigen (HBs) by ELISA

Description

Time Frame

1 month following primary immunization (at Month 3)

Title

Concentrations of Antibodies Against Hepatitis B Surface Antigen (HBs) by ELISA.

Description

Time Frame

1 month after the booster dose of DTPw-HBV/Hib vaccine (at Month 15)

Title

Concentrations of Antibodies Against Rotavirus Immunoglobulin A (Rotavirus IgA), by Rotarix Vaccination Status.

Description

Time Frame

1 month after the administration of the second vaccine dose (at Month 3)

Title

Concentrations of Antibodies Against Measles

Description

Concentrations of antibodies are presented as GMCs expressed as milli-International units per milliliter (mIU/mL).The cut-off of the assay is 150 mIU/mL.

Time Frame

1 month following administration of the 1st and 2nd vaccine dose (at Months 9 and 15)

Title

Anti-LytC IgA and Anti-PhtD IgA Antibodies Concentrations in Salivary Samples

Description

Time Frame

up to study end at Month 23 (24-27 months of age)

Title

Description

Time Frame

up to study end at Month 23 (24-27 months of age)

Title

Number of Subjects With Acquisition of New Streptococcus Pneumoniae and Haemophilus Influenzae Strains Identified in Nasopharyngeal Swabs

Description

Time Frame

up to study end at Month 23 (24-27 months of age)

Title

Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs).

Description

Time Frame

During the 4-day (Days 0-3) post-primary vaccination period across doses

Title

Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs).

Description

Time Frame

During the 4-day (Days 0-3) post-primary vaccination period across doses

Title

Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs).

Description

Time Frame

During the 4-day (Days 0-3) period following booster vaccination with Synflorix vaccine

Title

Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs).

Description

Time Frame

During the 4-day (Days 0-3) period following booster vaccination with Synflorix vaccine

Title

Number of Subjects With Unsolicited AEs.

Description

Time Frame

Within the 31-day (Days 0-30) post-primary vaccination period

Title

Number of Subjects With Unsolicited AEs.

Description

Time Frame

Within the 31-day (Days 0-30) post Synflorix booster vaccination period

Title

Number of Subjects With Serious Adverse Events (SAEs).

Description

Time Frame

From study start at Month 0 (6 weeks of age and above) up to study end at Month 23 (24-27 months of age)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Weeks

Maximum Age & Unit of Time

10 Weeks

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female subjects between, and including 6-10 weeks of age at the time of the first vaccination. Subjects for whom the investigator believes that their parent(s)/guardian(s) can and will comply with the requirements of the protocol. Written informed consent obtained from the parent(s)/guardian(s) of the child/ward. Free of any known or suspected health problems (as established by medical history and clinical examination before entering into the study). Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of the study vaccines, or planned use during the study period. A family history of hereditary immunodeficiency other than HIV infection. Major congenital defects or serious chronic illness other than HIV infection. For HIV infected infants: Moderately and severely symptomatic: stages III and IV according to latest version of WHO classification. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. Previous vaccination against diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, and/or Streptococcus pneumoniae. History of, or intercurrent, diphtheria, tetanus, pertussis, and Haemophilus influenzae type b disease. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. History of any neurological disorders or seizures. Acute disease at the time of enrolment. Babies for which weight for age is < 3rd percentile at Visit 1, using standard growth charts, with the exception of HIV infected infants for which the decision of enrolment was left to the investigator's discretion. Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal (GI) tract, intussusception (IS) or other medical condition determined to be serious by the investigator. Gastroenteritis within 7 days preceding the study vaccine administration (warrants deferral of vaccination).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Soweto

State/Province

Gauteng

ZIP/Postal Code

2013

Country

South Africa

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Citations:

PubMed Identifier

33245004

Citation

Nunes MC, Moreira M, Koen A, van Niekerk N, Jose L, Cutland CL, Francois N, Schoonbroodt S, Ruiz-Guinazu J, Yarzabal JP, Borys D, Schuerman L, Madhi SA. Bacterial nasopharyngeal carriage following infant immunization with pneumococcal conjugate vaccines according to a 2+1 schedule in children in South Africa: an exploratory analysis of two clinical trials. Expert Rev Vaccines. 2020 Dec;19(12):1177-1189. doi: 10.1080/14760584.2020.1853533. Epub 2020 Dec 21.

Results Reference

derived

PubMed Identifier

32035706

Citation

Madhi SA, Moreira M, Koen A, van Niekerk N, de Gouveia L, Jose L, Cutland CL, Francois N, Schoonbroodt S, Ruiz-Guinazu J, Yarzabal JP, Borys D, Schuerman L. Impact of HIV status and vaccination schedule on bacterial nasopharyngeal carriage following infant immunisation with the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine in South Africa. Vaccine. 2020 Feb 28;38(10):2350-2360. doi: 10.1016/j.vaccine.2020.01.062. Epub 2020 Feb 5.

Results Reference

derived

PubMed Identifier

28425818

Citation

Madhi SA, Koen A, Jose L, Moreira M, van Niekerk N, Cutland C, Francois N, Ruiz-Guinazu J, Yarzabal JP, Borys D, Schuerman L. Immunization with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) according to different schedules in infants in South Africa: a phase III trial. Expert Rev Vaccines. 2017 Jun;16(6):641-656. doi: 10.1080/14760584.2017.1321990.

Results Reference

derived

PubMed Identifier

28079828

Citation

Madhi SA, Koen A, Jose L, van Niekerk N, Adrian PV, Cutland C, Francois N, Ruiz-Guinazu J, Yarzabal JP, Moreira M, Borys D, Schuerman L. Vaccination with 10-valent pneumococcal conjugate vaccine in infants according to HIV status. Medicine (Baltimore). 2017 Jan;96(2):e5881. doi: 10.1097/MD.0000000000005881.

Results Reference

derived

Links:

URL

https://www.clinicalstudydatarequest.com

Description

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Available IPD and Supporting Information:

Available IPD/Information Type

Annotated Case Report Form

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

111634

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Clinical Study Report

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

111634

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Study Protocol

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

111634

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Dataset Specification

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

111634

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Statistical Analysis Plan

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

111634

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Individual Participant Data Set

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

111634

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Informed Consent Form

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

111634

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Learn more about this trial

Primary and Booster Vaccination Study With a Pneumococcal Vaccine in HIV Infected, HIV Exposed Uninfected and HIV Uninfected Children 6 to 10 Weeks of Age.

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